As many would-be biotech entrepreneurs have learned, one of the scariest things about bringing a new biomedical technology into the world is when an unexpected and very public problem crops up, especially during clinical trials. You can’t tell if you’ve merely hit a bump in the road or run smack into a brick wall. At the moment of impact, they feel much the same.

The road to gene therapy, which has been nothing if not rocky over the last two decades, hit another one of those sickening bumps last September, when word spread from Philadelphia that a fatality had occurred in a gene therapy trial at the University of Pennsylvania’s Institute for Human Gene Therapy. Eighteen-year-old Jesse Gelsinger, according to university officials, died four days after receiving experimental treatment for a genetic disorder known as ornithine transcarbamylase (OTC) deficiency. In reporting the episode, publications like the Wall Street Journal suggested that the death was “raising new questions” about a beleaguered technology.

As readers of my book A Commotion in the Blood already know, I’ve cast a pretty jaundiced eye on the extraordinary hype and the extraordinarily unimpressive results that have come out of this area of research so far. The field’s pioneering practitioners seemed at least as interested in making history as in making patients better when the first authorized attempt at gene transfer occurred at the National Institutes of Health in 1989; more than a decade later, after hundreds of clinical trials, there has yet to be published a single study
that unambiguously demonstrates gene therapy works. It is typical of the headlong (or is it headstrong?)ambition of the field that we now learn of other deaths in clinical trials, which went unreported to the NIH at the discretion of the investigators (many of whom relinquish the moral high ground when they have financial interests in the work).

For all that, this technology has immense intuitive appeal. The idea of turning engineered viruses into biological smugglers, using their evolutionarily honed ability to infiltrate cells and insinuate therapeutic DNA into the cell’s chromosome, strikes almost everyone as an elegant and supremely clever way to correct enzymatic deficiencies and other genetic diseases. Indeed, the swelling list of genes identified by the
Human Genome Project provides an attractive list of potential cargo for these viral vectors to deliver.